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New Hope  is taken as the key exchange to share secret information. ... New Hope is an ephemeral key exchange protocol proposed in 2015  . It offers 128-bit postquantum security. ...doi:10.1109/access.2020.3040324 fatcat:tkeqfby2jnattkm4me5cstfj4u
This study aimed to assess the experiences of police officers facing a public inquiry following a traumatic work-related event. Interviews of 11 officers were analyzed for qualitative themes. Quantitative measures of social support and current level of distress were compared with a sample of paramedics and firefighters matched for traumatic experiences and involvement in postmortem reviews. In response to the events leading to the inquiry, reactions consistent with posttraumatic stress weredoi:10.1093/brief-treatment/mhg030 fatcat:uq5e4wudxzdhhcujg4svm3qhzu
more »... on. Review processes were typically prolonged. Common negative consequences included lack of professional advancement, strained family relations, and inaccurate and sensationalized media attention. An important mediating factor was the quality of organizational support. Following the inquiry, police officers rarely felt a sense of vindication and frequently reported a diminished sense of commitment to their work. In conclusion, review processes following work-related trauma have many negative consequences for police officers. Suggestions for intervention include crisis intervention services with officers, organizational development, and the enhancement of peer support programs. [Brief Treatment and Crisis Intervention 3:383-396 (2003)]
Harding, Gina E. Migneco, Sina S. Rahini and Hope B. Coleman in Annals of Pharmacotherapy ...doi:10.25384/sage.14703326.v1 fatcat:giif7ol7nzbyfhnfvg4ncho35u
Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signatures can accurately predict clinical response in individuals treated with these drugs. Notably, signatures developed to predict response to individual agents, when combined, coulddoi:10.1038/nm1491 pmid:17057710 fatcat:lishflvcfnhojbxtniwcagdnji
more »... predict response to multidrug regimens. Finally, we integrated the chemotherapy response signatures with signatures of oncogenic pathway deregulation to identify new therapeutic strategies that make use of all available drugs. The development of gene expression profiles that can predict response to commonly used cytotoxic agents provides opportunities to better use these drugs, including using them in combination with existing targeted therapies. Numerous advances have been achieved in the development, selection and application of chemotherapeutic agents, sometimes with remarkable clinical successes-as in the case of treatment for lymphomas or platinum-based therapy for testicular cancers 1 . In addition, in several instances, combination chemotherapy in the postoperative (adjuvant) setting has been curative. However, most people with advanced solid tumors will relapse and die of their disease. Moreover, administration of ineffective chemotherapy increases the probability of side effects, particularly those from cytotoxic agents, and of a consequent decrease in quality of life 1,2 . Recent work has demonstrated the value in using biomarkers to select individuals for various targeted therapeutics, including tamoxifen, trastuzumab and imatinib mesylate. In contrast, equivalent tools to select those most likely to respond to the commonly used chemotherapeutic drugs are lacking 3 . With the goal of developing genomic predictors of chemotherapy sensitivity that could direct the use of cytotoxic agents to those most likely to respond, we combined in vitro drug response data, together with microarray gene expression data, to develop models that could potentially predict responses to various cytotoxic chemotherapeutic drugs 4 . We now show that these signatures can predict clinical or pathologic response to the corresponding drugs, including combinations of drugs. We further use the ability to predict deregulated oncogenic signaling pathways in tumors to develop a strategy that identifies opportunities for combining chemotherapeutic drugs with targeted therapeutic drugs in a way that best matches the characteristics of the individual. RESULTS A gene expression-based predictor of sensitivity to docetaxel To develop predictors of cytotoxic chemotherapeutic drug response, we used an approach similar to previous work analyzing the NCI-60 panel 4 from the US National Cancer Institute (NCI). We first identified cell lines that were most resistant or sensitive to docetaxel (Fig. 1a,b) and then genes whose expression correlated most highly with drug sensitivity, and used Bayesian binary regression analysis to develop a model that differentiates a pattern of docetaxel sensitivity from that of resistance. A gene expression signature consisting of 50 genes was identified that classified cell lines on the basis of docetaxel sensitivity (Fig. 1b, right) . In addition to leave-one-out cross-validation, we used an independent dataset derived from docetaxel sensitivity assays in a series of 30 lung and ovarian cancer cell lines for further validation. The significant correlation (P o 0.01, log-rank test) between the predicted probability of sensitivity to docetaxel (in both lung and ovarian cell lines) (Fig. 1c, left) and the respective 50% inhibitory concentration (IC 50 ) for docetaxel confirmed the capacity of the docetaxel predictor to predict sensitivity to the drug in cancer cell lines ( Supplementary Fig. 1 online) . For each set of cell lines, the accuracy exceeded 80%. Finally, we made use of a second independent
The links between sexual violence, genitoanal injury, and HIV are understudied but potentially significant for understanding the epidemic's disproportionate impacts on young women and girls, particularly in sub-Saharan Africa, other hyperendemic areas, and conflict-affected regions. bringing together an interdisciplinary group of researchers, clinicians, and policy makers to identify knowledge needs and gaps in three key areas: (1) the role of genitoanal injury on HIV transmission, acquisition,doi:10.1089/aid.2012.0273 pmid:22953712 pmcid:PMC3485903 fatcat:yaaxa7v4afasjbmu7jnxlbh5gy
more »... and pathogenesis; (2) the influence of sex and age-related anatomic characteristics on HIV transmission, acquisition, and pathogenesis; and (3) the role of heterosexual anal intercourse in HIV transmission. This article reflects the consensus that emerged from the Greentree Meeting regarding priority scientific research questions in these three areas, associated data collection and measurement challenges and opportunities, and implications for policy and practice.
Matare, Hope C. Craig, Stephanie L. Martin, Rosemary A. Kayanda, Gina M. Chapleau, Rachel Bezner Kerr, Kirk A. Dearden, Luitfrid P. Nnally and Katherine L. Dickin in Food and Nutrition Bulletin ... You all are proud fathers of a young baby, so please tell us … MT1.B1 -What hopes do you have for your baby? MT1.B2 -What do you hope your baby to be when s/he grows up?" ... I really encourage you to try the new recommendations to improve breastfeeding and hope the new ideas go well for you. ...doi:10.25384/sage.8100353.v1 fatcat:sgy5ykxfj5c3dbdtr53y3m6w3e
Matare, Hope C. Craig, Stephanie L. Martin, Rosemary A. Kayanda, Gina M. Chapleau, Rachel Bezner Kerr, Kirk A. Dearden, Luitfrid P. Nnally and Katherine L. Dickin in Food and Nutrition Bulletin ...doi:10.25384/sage.8100356.v1 fatcat:aguewipfibhdtfupnzfre472h4
Marking functionally distinct neuronal ensembles with high spatiotemporal resolution is a key challenge in systems neuroscience. We recently introduced CaMPARI, an engineered fluorescent protein whose green-to-red photoconversion depends on simultaneous light exposure and elevated calcium, which enabled marking active neuronal populations with single-cell and subsecond resolution. However, CaMPARI (CaMPARI1) has several drawbacks, including background photoconversion in low calcium, slowdoi:10.1038/s41467-018-06935-2 fatcat:zgj3wmb75zhwjaoy7uh3sy5yqq
more »... s and reduced fluorescence after chemical fixation. In this work, we develop CaMPARI2, an improved sensor with brighter green and red fluorescence, faster calcium unbinding kinetics and decreased photoconversion in low calcium conditions. We demonstrate the improved performance of CaMPARI2 in mammalian neurons and in vivo in larval zebrafish brain and mouse visual cortex. Additionally, we herein develop an immunohistochemical detection method for specific labeling of the photoconverted red form of CaMPARI. The anti-CaMPARI-red antibody provides strong labeling that is selective for photoconverted CaMPARI in activated neurons in rodent brain tissue.
Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also have in vitro antifungal activity that includes Cryptococcus neoformans . Flubendazole (a benzimidazole) has been reformulated by Janssendoi:10.1128/aac.01909-17 pmid:29311092 pmcid:PMC5913986 fatcat:zbteyq4pazhovpg2iod5qxr6si
more »... a as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis. We investigated the in vitro activity, the structure-activity-relationships, and both in vitro and in vivo pharmacodynamics of flubendazole for cryptococcal meningitis. Flubendazole has potent in vitro activity against Cryptococcus neoformans , with a modal MIC of 0.125 mg/liter using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. Computer models provided an insight into the residues responsible for the binding of flubendazole to cryptococcal β-tubulin. Rapid fungicidal activity was evident in a hollow-fiber infection model of cryptococcal meningitis. The solid drug nanodispersion was orally bioavailable in mice with higher drug exposure in the cerebrum. The maximal dose of flubendazole (12 mg/kg of body weight/day) orally resulted in an ∼2 log 10 CFU/g reduction in fungal burden compared with that in vehicle-treated controls. Flubendazole was orally bioavailable in rabbits, but there were no quantifiable drug concentrations in the cerebrospinal fluid (CSF) or cerebrum and no antifungal activity was demonstrated in either CSF or cerebrum. These studies provide evidence for the further study and development of the benzimidazole scaffold for the treatment of cryptococcal meningitis.
Heart Transplantation The hope for all patients with end-stage heart failure is to survive successful heart transplantation. However, the timing is, naturally, unpredictable. ... to serve as a roadmap for care teams looking to incorporate PPC in their practice. the HF journey and hopes to serve as a roadmap for care teams looking to incorporate PPC in their practice. ...doi:10.3390/children8060468 fatcat:njve34ocrvfv3avgkz5vfh5mvq
Context-Terminally ill hospitalized patients and their families consistently rank effective communication and shared decision-making among their top priorities. Advance Practice Providers such as Physician Assistants (PAs) are increasingly providing care in the hospital setting and are often called to communicate with patients and families. A first step to improving PA communication is to better understand PAs' current experiences in their daily practices. Objectives-This study aimed todoi:10.1016/j.jpainsymman.2017.03.011 pmid:28479409 pmcid:PMC5512421 fatcat:22daj3yjqnb25is5xz6rswqtoy
more »... 1) roles PAs serve in communicating with terminally ill patients/families; 2) PAs' attitudes and opinions about communication roles and 3) perceived barriers and facilitators of communication with patients/families in the hospital setting. Methods-Five focus groups were conducted with PAs practicing on adult medical services at three acute care hospitals of an academic medical center in the Bronx, NY. An open-ended question guide was used. An inductive thematic analysis strategy was used to examine the data from transcribed audiotapes of focus group sessions to identify emergent concepts and themes.
Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymaldoi:10.3390/ijerph13010010 pmid:26703648 pmcid:PMC4730401 fatcat:njbvvgnbwzcknpw5rfirt33ptq
more »... ransition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused á 3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.
Incisional hernia is a frequent complication of midline laparotomy and enterostomal creation and is associated with high morbidity, decreased quality of life, and high costs. The International Symposium on Incisional Hernia Prevention was held October 19 -20, 2017, at the InterContinental Hotel in San Francisco, CA, hosted by the Department of Surgery, University of California, San Francisco. One hundred and three attendees included general and plastic surgeons from 9 countries, includingdoi:10.1016/j.surg.2018.02.020 pmid:29705098 fatcat:tofnrowoujhhbb2pi5xgvcki6e
more »... pal participants for several of the seminal studies in the field. Over the course of the 2-day meeting, there were 38 oral presentations, 3 keynote lectures, and 2 panel discussions. The Symposium was a combination of new information but also a comprehensive review of the existing data so as to assess the current state of the * Corresponding author: 2 H.W. Harris et al. / Surgery 0 0 0 (2018) 1-8 JID: YMSY [m5G; April 25, 2018;7:6 ] field and to set the stage for future research. Further, the Symposium sought to increase awareness and thus emphasize the importance of preventing the formation of incisional and enterostomal hernias. ARTICLE IN PRESS Epidemiology, pathogenesis & economics of incisional hernias Although the overall epidemiology of incisional hernias has been well delineated, the fundamental pathogenesis of this postoperative complication and how to identify patients at increased risk remain topics of active interest and research. Furthermore, the substantial economic impact of the condition, estimated to be > $3 billion annually in the US, is garnering more attention. A systematic review of factors affecting midline incisional hernia rates A comprehensive review of the literature, including the largest meta-regression analysis published to date on the subject, identified several factors that independently increased the risk of midline incisional hernia. The factors included increasing age, obesity (or upper midline incision alone), abdominal aortic aneurysm surgery, previous laparotomy, and previous incisional hernia repair. 1 Notably, there was no evidence that suture type (absorbable vs nonabsorbable) affects the rate of hernia formation. The overall pooled incidence of incisional hernias of midline wounds at 2 years was 12.8% with a wide range (0% -36%).
Overuse injuries have a significant impact on United States military service members, but research to date has been limited in its ability to assess occupational and behavioral risk factors. Hypothesis/Purpose: To prospectively identify risk factors for the development of lower extremity tendinopathy and plantar fasciitis in United States military personnel. Study Design: Descriptive epidemiology study. Methods: Baseline data from the Millennium Cohort Study, a long-term observational cohort ofdoi:10.1177/2325967113492707 pmid:26535232 pmcid:PMC4555504 fatcat:4cqhnf7w6fdrdfumwi6qvifyzu
more »... military personnel, were utilized. Service members were enrolled in the cohort in 2001, 2004, and 2007. A total of 80,106 active-duty personnel were followed over 1 year for the development of patellar tendinopathy, Achilles tendinopathy, and plantar fasciitis. Regression analyses were used to estimate significant associations between each tendinopathy, plantar fasciitis, and demographic, behavioral, and occupational characteristics. Results: Using medical records, 450 cases of Achilles tendinitis, 584 cases of patellar tendinopathy, and 1228 cases of plantar fasciitis were identified. Recent deployment was associated with an increased risk for developing plantar fasciitis (adjusted odds ratio [AOR], 1.27; 95% confidence interval [CI], 1.04-1.56). Moderate weekly alcohol consumption was marginally associated with an increased risk for Achilles tendinopathy (AOR, 1.33; 95% CI, 1.00-1.76). Overweight or obese individuals were more likely to develop Achilles tendinopathy and plantar fasciitis. Conclusion: Lower extremity tendinopathies and plantar fasciitis are common among military service members, and this study identified several modifiable risk factors for their occurrence. These potential risk factors could serve as the focus for future preventive and intervention studies.
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